Unveiling Immune Metabolic Mechanisms in Bladder Cancer: Spatial Profiling Identifies ZFP36 as a Therapeutic Target

Treatment of bladder cancer (BLCA) is currently facing formidable challenges due to its high heterogeneity and immune evasion. In this study, we utilize spatial metabolomics (SM) and spatial transcriptomics (ST) to systematically analyze and visualize metabolic and transcriptional landscapes of BLCA. Correlation analysis reveals significant metabolic and transcriptional differences among tumor regions, shedding light on the heterogeneity and immune-related metabolic reprogramming mechanisms in BLCA. Further studies identify ZFP36 as a potential immunotherapeutic marker, with its higher expression correlating with poor prognosis in BLCA patients. Mechanistically, ZFP36 mediates the mRNA decay of key immune regulatory genes, including C1QBP, thereby suppressing T-cell activation and cytotoxicity. Notably, the combination of ZFP36 knockout and anti-PD-1 therapy demonstrated synergistic antitumor effects, suggesting that targeting ZFP36 may offer a promising therapeutic strategy for BLCA treatment. In summary, this study, through integrated multi-omics analysis, unveils the immune metabolic regulatory mechanisms of BLCA and provides crucial molecular targets for immunotherapy. Overall design: Validation of immunometabolic reprogramming in bladder cancer by association analysis of spatial transcriptomics and spatial metabolomics